Startup Unveils Nanosensors to Track Enzyme Reactions

Scott Nelson, left, and Nathaniel Kallmyer work in the laboratory of Zymosense, a startup company based in the Iowa State University Research Park. Iowa State University/Christopher Gannon.
Scott Nelson, left, and Nathaniel Kallmyer work in the laboratory of Zymosense, a startup company based in the Iowa State University Research Park. Iowa State University/Christopher Gannon.

Quick look

A startup company called Zymosense is developing and marketing nanosensors invented in Nigel Reuel's Iowa State lab. The new tools will help industries track and improve the enzymes used in biotechnology, medicine, drug development, food production and other industrial and everyday applications.

AMES, Iowa - The website video shows a carbon nanotube - a lattice structure measured in billionths of a meter - floating in a solution and glowing red when hit by laser light.

A long strand of a protein substrate, its atoms pictured in green, black and gray, winds around the tube. Floating in from the top is a swirling yellow, purple and magenta ribbon diagram of a protease, a type of enzyme that breaks down proteins. The enzyme quickly snips the protein. There's a chemical reaction. Suddenly new products are floating around.

And, the fluorescing nanotube goes dark.

Track those light quenches with special readers, and you can measure enzyme activity. And you can do it 62% quicker and with half the steps of existing assays, or lab tests to measure various properties of materials.

That's the big idea behind Zymosense, "The Nanoassay Company," a startup that's spinning off technology developed in the lab of Nigel Reuel, the Stanley Chair in Interdisciplinary Engineering at Iowa State University and co-founder and chairman of the company.

It all started with Reuel asking a new doctoral student in his research group, "What if?"

'No enzymes - no life'

After his graduate school days at the Massachusetts Institute of Technology, Reuel went to work for DuPont as a research investigator and then a corporate technology scout with a charge to "find interesting things to enable new business."

Well, part of DuPont's business was working with proteins and designing new enzymes, the biological catalysts that drive all kinds of chemical reactions without being eaten up by the process so they can be reused. They're vital to digestion, disease management and much more. As a Zymosense fact sheet says, "No enzymes - no life."

Enzymes also have lots of industrial and everyday uses in biotechnology, medical applications, drug development and food production. One example is from your laundry room: cold water detergents use engineered enzymes to clean without the extra help from heat.

But working with enzymes was a chore. The step-by-step procedures and the reagents used to measure enzyme activity were complex and required staff and time.

"That equals your money," Reuel said of his message to businesses and the motivation to find a better way.

So, when he arrived at Iowa State in 2016, he asked one of his first graduate students to start exploring a better way to measure enzyme activity. Maybe the fluorescent sensors Reuel worked with as a graduate student could help?

"I started with Nigel asking a 'What if?" said Nathaniel Kallmyer, who earned his Iowa State doctorate in 2021 and is now a co-founder and chief technology officer for Zymosense. "What would happen if you put a protein on the surface of a nanotube and introduced an enzyme?"

You get a functioning biosensor, Kallmyer discovered.

"I was surprised by how quickly it worked," he said. "It worked the first time."

But, Reuel said, there was still lots of work ahead. The researchers had to understand the process, refine it for different enzymes and scale it up for commercial use.

'The future of biochemical sensing'

Nathaniel Kallmyer holds a bottle of Zymosense nanosensors. Iowa State University/Christopher Gannon.
Nathaniel Kallmyer holds a bottle containing Zymosense nanosensors. Iowa State University/Christopher Gannon.

Stop by the Zymosense office and laboratory at the Iowa State University Research Park and it's not long before Scott Nelson, the startup's CEO, heads back to the lab and picks up what looks like a bulb for a night light.

There's a grayish fluid sloshing around inside.

"You'll never hold something like this again the rest of your life," he said. "There's a trillion single-walled carbon nanotubes in there."

There's also a 2020 U.S. patent in there. It's for "optical nanosensors for hydrolytic enzyme characterization." The Iowa State University Research Foundation filed for patent protection on the nanosensors and related innovations starting in 2018 and licensed the technologies to Zymosense in 2022.

Reuel and Kallmyer had founded Zymosense to commercialize the technology in 2021.

They progressed through Iowa State's startup ecosystem, including the campus site of the U.S. National Science Foundation's Innovation Corps, plus the Startup Factory and Go-To-Market programs. Reuel met Nelson through mentoring projects with the Pappajohn Center for Entrepreneurship.

They've also won support from the federal Small Business Innovation Research program and the Iowa Economic Development Authority. In all, they've raised $850,000 in grants and awards for research and development. There are also five investors.

All of that has allowed the company to grow to five employees working with two technical advisors.

"Zymosense is kind of the poster child for everything Iowa State is trying to do," Nelson said. "They explored all of these resources."

Nelson, an Iowa State graduate who has business experience spanning General Motors in Detroit and software startups in Denver, said he expects the company's functionalized nanosensors will be on sale early next year. A typical product would be nanosensors in 5 milliliters of liquid for $499.

Kallmyer said one bottle could do up to about 2,000 tests.

As the company website says, "The future of biochemical sensing arrives in 2026."

And as Reuel, who has founded four companies and co-teaches a "Deep Tech Venture Creation" course, likes to say about startup ideas: "All good innovation comes in response to some problem or need."

Turns out there all kinds of industries that need to track and improve their enzymatic workforce.

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